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Nutrition and Disease

Retinoic Acid Therapy Attenuates the Severity of Tuberculosis While Altering Lymphocyte and Macrophage Numbers and Cytokine Expression in Rats Infected with Mycobacterium tuberculosis^1–3,

⁴ Mycobacterial Reference Center, Research Institute of Tuberculosis, Tokyo 204-0022 Japan; and ⁵ Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802

^* To whom correspondence should be addressed. E-mail: sugawara{at}jata.or.jp.

Because retinoic acid (RA) exerts a stimulatory effect on macrophages and tubercle bacilli target alveolar macrophages, the therapeutic potential of RA was examined in rats with tuberculosis. In the main study, 15 rats were randomized to treatment with oil (control) or RA,100 µg/100 g body weight per dose, given 3 times weekly for 3 and 5 wk after infection with Mycobacterium tuberculosis strain H37Rv. There was a significant difference in the severity of tuberculosis histopathology between control and RA-treated rats, and oral administration of RA decreased the number of colony-forming units (CFU) in both lung and spleen at 3 and 5 wk after H37Rv infection (P < 0.005). CD4-positive and CD8-positive T cells, natural killer cells, and CD163-positive macrophages increased (P < 0.05) in the infected lung tissues of RA-treated rats. Expression of IFN and inducible nitric oxide synthetase messenger RNA (mRNA) was higher in the infected lung tissues of RA-treated rats than in control rats. Alveolar macrophages from rats treated in vivo with RA and infected in vitro with M. tuberculosis showed significantly higher expression of TNF and IL-1ß mRNA than macrophages in control rats. To our knowledge, this is the first reported study to demonstrate that orally administered RA significantly inhibits the in vivo growth of M. tuberculosis and the development of tuberculosis.